The present invention generally relates to an apparatus and related method for therapeutically treating and/or analyzing conditions of the inner ear. More particularly, the invention involves a multi-functional medical apparatus for use in connection with the middle and inner ear in which the apparatus is capable of (1) delivering therapeutic agents including various medicines in fluid or solid-powder form to internal ear (e.g. inner ear) structures; (2) extracting, withdrawing, or exchanging fluid materials from the inner ear; (3) transferring fluid materials into and out of the inner ear via the round window membrane so that items [1] and [2] can be accomplished; (4) enabling middle and inner ear structures to be electrophysiologically monitored using electrocochleography (xe2x80x9cECoGxe2x80x9d) procedures; (5) altering the permeability of the round window membrane in the ear for a variety of therapeutic purposes with drugs, chemical agents, or iontophoresis; and (6) creating a discrete sealed or non-sealed xe2x80x9cfluid-receiving zonexe2x80x9d within the round window niche so that fluid materials can be transferred into and out of the inner ear via the adjacent round window membrane in a controlled and site-specific manner.
In order to treat ear disorders, it may often be necessary to deliver therapeutic agents to various ear tissues in a controlled, safe, and efficient manner. For example, a variety of structures have been developed which are capable of delivering/administering therapeutic agents into the external auditory canal of the outer ear. U.S. Pat. No. 4,034,759 to Haerr discloses a hollow, cylindrical tube manufactured of sponge material (e.g. dehydrated cellulose) which is inserted into the external auditory canal of a patient. When liquid medicines are placed in contact with the tube, it correspondingly expands against the walls of the auditory canal. As a result, accidental removal of the tube is prevented. Furthermore, medicine materials absorbed by the tube are maintained in contact with the walls of the external auditory canal for treatment purposes. Other absorbent devices designed for treatment of the external auditory canal and related tissue structures are disclosed in U.S. Pat. No. 3,528,419 to Joechle, U.S. Pat. No. 4,159,719 to Haerr, and U.S. Pat. No. 2,642,065 to Negri. The Negri patent specifically describes a medicine delivery device with an internally-mounted, frangible medicine container which, when broken, releases liquid medicines into an absorbent member.
However, the delivery of therapeutic agents in a controlled and effective manner is considerably more difficult with respect to tissue structures of the inner ear (e.g. those portions of the ear surrounded by the otic capsule bone and. contained within the temporal bone which is the most dense bone tissue in the entire human body). The same situation exists in connection with tissue materials which lead into the inner ear (e.g. the round window membrane). Exemplary inner ear tissue structures of primary importance for treatment purposes include but are not limited to the cochlea, the endolymphatic sac/duct, the vestibular labyrinth, and all of the compartments (and connecting tubes) which include these components. Access to the above-described inner ear tissue regions is typically achieved through a variety of structures, including but not limited to the round window membrane, the oval window/stapes footplate, the annular ligament, the otic capsule/temporal bone, and the endolymphatic sac/endolymphatic duct, all of which shall be considered xe2x80x9cmiddle-inner ear interface tissue structuresxe2x80x9d as described in greater detail below. Furthermore, as indicated herein, the middle ear shall be defined as the physiological air-containing tissue zone behind the tympanic membrane (e.g. the ear drum) and ahead of the inner ear.
The inner ear tissues listed above are of minimal size and only readily accessible through microsurgical procedures. In order to treat various diseases and conditions associated with inner ear tissues, the delivery of medicines to such structures is often of primary importance. Representative medicines which are typically used to treat inner ear tissues include but are not limited to urea, mannitol, sorbitol, glycerol, lidocaine, xylocaine, epinephrine, immunoglobulins, sodium chloride, steroids, heparin, hyaluronidase, aminoglycoside antibiotics (streptomycin/gentamycin), antioxidants, neurotrophins, nerve growth factors, various therapeutic peptides, and polysaccharides. Of particular interest in this list are compounds which are used to alter the permeability of the round window membrane within the ear using, for example, hyaluronidase and iontophoretic techniques (defined below). Likewise, treatment of inner ear tissues and/or fluid cavities may involve altering the pressure, volume, electrical activity, and temperature characteristics thereof. Specifically, a precise balance must be maintained with respect to the pressure of various fluids within the inner ear and its associated compartments. Imbalances in the pressure and volume levels of such fluids can cause various problems, including but not limited to conditions known as endolymphatic hydrops, endolymphatic hypertension, perilymphatic hypertension, perilymphatic hydrops, perilymphatic fistula, intracochlear fistula, Meniere""s disease, tinnitus, vertigo, hearing loss related to hair cell or ganglion cell damage/malfunction, and ruptures in various membrane structures within the ear.
Of further interest regarding the delivery of therapeutic agents to the middle ear, inner ear, and middle-inner ear interface tissue structures are a series of related and co-owned patents, namely, U.S. Pat. Nos. 5,421,818; 5,474,529, and 5,476,446 all to Arenberg. Each of these patents discloses a medical treatment apparatus designed to deliver fluid materials to internal ear structures. U.S. Pat. No. 5,421,818 describes a treatment system which includes a tubular stem attached to a reservoir portion with an internal cavity designed to retain a supply of therapeutic fluid compositions therein. The side wall of the reservoir portion further comprises fluid transfer means (e.g. pores or a semi-permeable membrane). Contact between the fluid transfer means and the round window membrane in a patient allows fluid materials to be delivered on-demand to the round window membrane, followed by diffusion of the fluid materials through the membrane into the inner ear. U.S. Pat. No. 5,474,529 involves a therapeutic treatment apparatus with a plurality of reservoir portions (e.g. a first and a second reservoir portion in a preferred embodiment) which are connected to multiple tubular stems that are designed for implantation into the endolymphatic sac and duct using standard microsurgical techniques. Finally, U.S. Pat. No. 5,476,446 discloses a therapeutic treatment apparatus which includes a reservoir portion for retaining liquid medicine materials therein, a first tubular stem on one side of the reservoir portion, and a second tubular stem on the opposite side of the reservoir portion. The second stem is designed to reside within the external auditory canal of a patient lateral to the ear drum, while the first stem is sized for placement within an opening formed in the stapes footplate/annular ligament so that medicine materials in fluid form can be delivered into the inner ear from the reservoir portion (which resides in the middle ear cavity medial to the ear drum).
A different approach for transferring materials into and out of the inner ear via the round window membrane/round window niche is disclosed in co-owned pending U.S. patent application Ser. No. 08/874,208 filed on Jun. 13, 1997. This application describes a system in which one or more fluid transfer conduits are provided which are operatively connected to a xe2x80x9ccover memberxe2x80x9d that is designed for placement on top of the niche (e.g. at its point of entry) or within the niche. The cover member is used to create a xe2x80x9cfluid-receiving zonexe2x80x9d (or xe2x80x9cinner ear fluid transfer spacexe2x80x9d) which is partially or entirely sealed in order to facilitate fluid transfer into and out of the inner ear. In one embodiment, the cover member consists of a thin, solid, plate-like structure that is secured in position on top of the niche at its point of entry as previously noted. Alternatively, the cover member may comprise a portion of flexible and compressible material which, during placement within the round window niche, is compressed and thereafter allowed to expand once the portion of compressible material is positioned within the niche. As a result, the cover member can engage the internal side wall of the round window niche, thereby creating the fluid-receiving zone (xe2x80x9cinner ear fluid transfer spacexe2x80x9d) between the compressible cover member and the round window niche. Representative materials used to construct the portion of compressible material associated with the cover member in this particular embodiment optimally involve foam-type products including but not limited to polyethylene foam, polyether foam, polyester foam, polyvinyl chloride foam, polyurethane foam, and sponge rubber (e.g. synthetic or natural), all of which are of the closed cell variety, with such materials being non-fluid-absorbent in accordance with the substantial lack of open cells therein. Specifically, the non-fluid-absorbent character of these materials results from the closed cell structure thereof which prevents fluid materials from being absorbed compared with open cell (absorbent) foam products.
Notwithstanding the systems described above, the present invention involves an improved medical treatment apparatus which provides many additional benefits. In accordance with the claimed invention, a unique and specially-designed treatment system is disclosed which is capable of performing a wide variety of basic functions including but not limited to (1) the repeatable and sustained active/passive delivery of therapeutic agents into the inner ear via diffusion or iontophoresis through the round window membrane; (2) the simultaneous measurement of inner ear electrical potentials (evoked or otherwise) using a technique known as xe2x80x9celectrocochleographyxe2x80x9d (hereinafter xe2x80x9cECoGxe2x80x9d) which is discussed in greater detail below; (3) the controlled withdrawal, exchange, or replacement of inner ear fluid materials via the round window membrane; (4) the delivery of therapeutic fluid compositions to the round window membrane in a manner which is rapid, efficient, controllable, and uses a minimal number of steps and procedures; (5) the transfer of therapeutic fluid compositions to the round window membrane in a highly site-specific manner; (6) the removal of fluid materials from the round window membrane in a localized fashion with minimal losses into adjacent tissue regions; (7) the ability to deliver and withdraw/exchange fluid materials from the inner ear at a precisely controlled rate which is readily undertaken using minimally-invasive surgical procedures; (8) accomplishment of all the above-described goals using a system which is readily applicable to multiple patients having different-sized ear structures; and (9) the ability to readily and instantaneously control placement of the claimed device within the middle ear regions (e.g. the round window niche) of a patient using a highly specialized inflatable xe2x80x9cplacement control systemxe2x80x9d which is of primary importance in the present invention. With respect to element number (9) listed above, this unique improvement enables the claimed apparatus to be more readily inserted and removed from a patient, and likewise secures the apparatus in position in a highly stable and rapid manner without requiring the use of adhesive compositions and other comparable attachment systems. Accordingly, the present invention represents an advance in the art of inner ear treatment, diagnosis, and medicine delivery as described in detail below.
It is an object of the present invention to provide an inner ear fluid transfer and diagnostic system (which can also be therapeutic in character) that enables the efficient delivery of fluid materials (e.g. therapeutic agents) to selected inner ear tissues and tissue regions.
It is another object of the invention to provide a fluid transfer and diagnostic system for treating the inner ear which allows the efficient removal or exchange of fluid materials from selected inner ear tissues and tissue regions.
It is another object of the invention to provide a fluid transfer and diagnostic system for treating the inner ear in which fluid materials are transferred/exchanged into and out of the inner ear directly through middle-inner ear interface tissue structures (e.g. the round window membrane).
It is another object of the invention to provide a fluid transfer and diagnostic system for treating the inner ear which enables the sustained transfer of fluid materials into and out of the inner ear (via the round window membrane) in a controlled, repeatable, and uniform manner.
It is another object of the invention to provide a fluid transfer and diagnostic system for treating the inner ear which facilitates the formation of a partially or completely sealed inner ear fluid-receiving, transfer, and/or exchange zone within the round window niche as further described below.
It is another object of the invention to provide a fluid transfer and diagnostic system for treating the inner ear which enables variable amounts of selected fluid materials to be transferred into and out of the inner ear including microgram/nanogram quantities of such materials (which is especially important when pharmacological agents are being delivered).
It is another object of the invention to provide a fluid transfer and diagnostic system for treating the inner ear which allows the delivery of fluid materials to the round window membrane and the removal of fluid materials therefrom in a highly site-specific manner while avoiding substantial leakage into surrounding tissue regions if desired.
It is a further object of the invention to provide a fluid transfer and diagnostic system for treating the inner ear which is of sufficiently small size to readily facilitate insertion of the claimed apparatus into a patient using minimally-invasive microsurgical procedures.
It is a further object of the invention to provide a fluid transfer and diagnostic system for treating the inner ear which, in one particular embodiment, enables the controlled delivery, exchange, and/or removal of fluid materials from the inner ear via middle ear structures (e.g. the round window membrane) in a manner wherein the fluid materials being delivered are maintained separately from the fluid materials being removed through the use of separate fluid delivery and fluid extraction passageways. As a result, efficient fluid transfer is accomplished while avoiding or minimizing cross-contamination between the fluids being removed and the fluids being delivered. This procedure is especially useful in situations involving drugs or other therapeutic agents which must be supplied in very precise amounts (e.g. microgram and/or nanogram quantities) or when such materials need to be transferred in a given sequence and at controlled time intervals.
It is an even further object of the invention to provide a fluid transfer and diagnostic system for treating the inner ear which has a subsystem (e.g. an electrode assembly) that is capable of delivering and receiving electrical signals (e.g. electrical potentials/electrical current) to and from the inner ear via the round window membrane or other middle ear structures.
It is an even further object of the invention to provide a fluid transfer and diagnostic system for treating the inner ear which, in a preferred embodiment, is capable of rapid placement within and removal from a patient with minimal frictional engagement between the claimed apparatus and the internal ear structures of the patient so that tissue abrasion and patient discomfort are avoided.
It is an even further object of the invention to provide a fluid transfer and diagnostic system for treating the inner ear which is capable of secure engagement within the round window niche of a patient in a minimally invasive manner and without requiring the use of adhesive compositions or other comparable auxiliary attachment systems.
It is an even further object of the invention to provide a fluid transfer and diagnostic system for delivering, receiving, or otherwise transferring fluid materials to and from the ear of a patient in connection with a variety of internal cavities within the ear (whether natural or man-made) in addition to the round window niche as discussed in greater detail below.
The present invention involves a highly effective and minimally-invasive apparatus and method for the controlled and site-specific transfer (e.g. xe2x80x9cmicrodosingxe2x80x9d) of physician-specified fluid materials into and out of the inner ear via the round window membrane (which is centrally located within the round window niche). The invention described herein offers numerous benefits and represents a significant advance in the art of middle and inner ear diagnosis/treatment. While the invention shall primarily be, discussed herein with reference to the round window membrane/round window niche, it shall also be applicable to other internal cavities within the ear which will become readily apparent from the discussion provided herein. Thus, all of the information presented below regarding use of the claimed apparatus (and all embodiments thereof) within the round window niche shall be incorporated by reference relative to other internal ear cavities (natural or man-made) without limitation. The following summary of the claimed apparatus and method represents a general overview of the invention which outlines the features of primary importance. A more detailed, specific, and enabling disclosure of the invention shall be presented later in the Detailed Description of Preferred Embodiments.
A first embodiment of the claimed invention involves a medical treatment apparatus and method for transferring fluid materials into and out of the inner ear of a human subject. via the round window membrane as previously noted. The apparatus first includes at least one fluid transfer conduit having a first end, a second end, and at least one internal passageway extending through the fluid transfer conduit from the first end to the second end (preferably in a continuous manner). Operatively connected (e.g. fixedly attached in an external, internal, other equivalent fashion as specifically defined below) to at least a portion of the fluid transfer conduit is an inflatable bladder member. The bladder member is preferably located at or adjacent to the first or second end of the conduit on the exterior surface thereof, and is sized for placement within the round window niche of the subject under consideration. The term xe2x80x9cplacementxe2x80x9d as used herein shall involve either partial or entire insertion of the bladder member into the ear cavity of interest (e.g. as much as is needed in accordance with the medical procedure of interest). As will be discussed in greater detail below, the round window niche comprises an internal side wall therein. To secure the apparatus in position within a patient so that fluid materials may be transferred into and out of the inner ear via the round window niche/round window membrane, the bladder member (when inflated and positioned within the round window niche) is designed to engage the internal side wall of the niche. As a result, the bladder member and the portion of the fluid transfer conduit attached thereto are effectively maintained within the niche.
By securing the bladder member and at least part of the fluid transfer conduit within the round window niche, a xe2x80x9cfluid-receiving zonexe2x80x9d is created inside the niche between the bladder member and the round window membrane which enables rapid, accurate, and site-specific fluid transfer to occur. At the same time, the apparatus is maintained in position in a minimally-invasive manner wherein primary contact/engagement between the tissues of the middle ear and the claimed apparatus only occurs when the bladder member is inflated. Using this approach, dynamic (e.g. sliding) frictional engagement between the claimed apparatus and the tissues of the middle ear during insertion of the apparatus is avoided which controls/reduces irritation, tissue damage, and patient discomfort.
In accordance with the specific system described above, the bladder member again creates a fluid-receiving zone between (1) the bladder member [the upper or external boundary of the fluid-receiving zone]; and (2) the round window membrane [the lower or internal boundary of the fluid-receiving zone]. In physiological terms, this fluid-receiving zone creates a xe2x80x9cfluid transfer spacexe2x80x9d between the bladder member and the round widow membrane within the round window niche. As discussed in considerable detail below, the claimed invention shall not be restricted to any particular size or shape characteristics in connection with the bladder member which may take a number of different forms. For example, the bladder member may be of a sufficiently small size or modified configuration so that, when it engages the internal side wall of the round window niche during inflation, it does not completely seal the fluid receiving zone between the bladder member and the round window membrane. In this particular embodiment, the bladder member may only engage one part of the internal side wall of the niche so that, if necessary in cases of excessive fluid pressure within the fluid-receiving zone, fluid materials can pass in a controlled manner outwardly from the zone (discussed further below).
However, in a preferred embodiment, the bladder member will be configured so that, when inflated, it will completely and circumferentially engage the internal side wall of the round window niche. As a result, a xe2x80x9csealedxe2x80x9d fluid-receiving zone is created between (1) the bladder member [the upper or external boundary of the sealed fluid-receiving zone]; and (2) the round window membrane [the lower or internal boundary of the sealed fluid-receiving zone]. By creating a sealed fluid-receiving zone in this manner, the precise delivery (e.g. microdosing) of medicine materials may be accomplished without any fluid leakage outside of the fluid-receiving zone which facilitates a greater degree of delivery precision. Other benefits associated with the creation of a sealed fluid-receiving zone include the maintenance of a controlled pressure environment in order to promote osmotic fluid transfer through the round window membrane as discussed below.
To form a sealed fluid-receiving zone within the round window niche using the inflatable bladder member, all of the components listed above are employed along with a bladder member which is annular (e.g. ring-shaped) so that it completely encircles the fluid transfer conduit at its point of attachment/connection to the conduit. By using a bladder member of this type (which is substantially ring-shaped with a central opening through which the fluid transfer conduit can pass), the bladder member can completely seal the fluid receiving zone by circumferentially engaging the internal side wall of the round window niche as previously discussed. However, the claimed invention shall not be restricted to a bladder member of any size or type which may be varied in accordance with the particular needs of the patient being treated and the desired placement position of the apparatus as determined by routine preliminary testing.
It should also be noted that, unless otherwise stated herein, the present invention and its various embodiments shall not be limited to any particular construction materials. Nonetheless, in a preferred and optimum embodiment, the bladder member will be manufactured from a biologically-inert, medical-grade elastomeric (stretchable) material selected from the group consisting of polyurethane, latex, silicone rubber, and other comparable commercially-available materials which have similar characteristics. Again, a number of different compositions may be employed for this purpose provided that they are capable of stretching sufficiently to achieve the required degree of inflation relative to the round window niche or other middle ear structure/cavity as discussed below. Regarding inflation of the bladder member, at least one xe2x80x9cinflation fluidxe2x80x9d is pumped into the bladder member for this purpose. The term xe2x80x9cfluidxe2x80x9d as used herein shall encompass either a gas, a liquid, a gel, or mixtures thereof with this term not being restricted to any particular media materials.
As previously noted, the inflatable bladder member is exteriorly attached to the fluid transfer conduit in a preferred and optimum embodiment. The term xe2x80x9cexteriorly attachedxe2x80x9d and xe2x80x9coperatively connectedxe2x80x9d shall encompass a wide variety of structural configurations including but not limited to adhesive affixation of the bladder member in position on the outer/exterior surface of the fluid transfer conduit. The foregoing phrase shall also encompass a situation in which the bladder member is integrated by molding, heat sealing, and other processes into the side wall of the fluid transfer conduit so that the bladder member forms the outer surface of the conduit which may then be inflated as indicated above. Thus, regardless of the structural configuration which is employed, the bladder member shall be considered xe2x80x9coperatively connectedxe2x80x9d to the fluid transfer conduit as long as it is capable of being inflated in a manner which allows the bladder member to directly engage the internal side wall of the round window niche (or other internal cavity of the ear) so that the conduit can be maintained in a precise and secure position therein. Likewise, the bladder member is operatively connected to the fluid transfer conduit at a position thereon which allows the fluid materials of interest (e.g. compositions transferred to and from round window niche or other desired ear cavity) to freely pass into and out of said apparatus without blockage thereof by the bladder member. This goal is accomplished in a preferred and non limiting embodiment by placement of the bladder member at a chosen location between the first and second ends of the fluid transfer conduit (e.g. on or within the outer surface thereof) or at any other location wherein the bladder member does not entirely block the fluid flow passageway(s) through the fluid transfer conduit as discussed further below. More specifically, the bladder member is preferably oriented whereby it is axially and/or laterally displaced from the fluid flow passageway(s) as shown in the accompanying drawing figures so that the bladder member does not entirely block, plug, or seal such passsageway(s).
All of the embodiments described above (including those with different bladder configurations) may likewise include an xe2x80x9celectrical potential transmission systemxe2x80x9d operatively connected to the fluid transfer conduit. The a term xe2x80x9coperatively connectedxe2x80x9d as used in connection with the electrical potential transmission system can encompass a situation in which this component is attached to the outer/exterior surface of the fluid transfer conduit using adhesive affixation methods, passed through the fluid transfer conduit within one of the passageways therein (including the use of a separate, dedicated passageway for this purpose) or directly incorporated (e.g. molded) into one of the walls of the fluid transfer conduit with all of these connection methods being considered equivalent. The electrical potential transmission system is used to transmit electrical potentials into and out of the inner ear, preferably through the round window membrane. The term xe2x80x9cpotentialxe2x80x9d as used herein shall be broadly construed to encompass any type of electrical signal, current, voltage, or impulse regardless of form, magnitude, or origin. In a preferred embodiment discussed in substantial detail below, the electrical potential transmission means will consist of an elongate conductive member (e.g. a metallic wire or strip with a ball, loop, mushroom, flat, or spoon-shaped tip). By placing at least a portion of the elongate conductive member (e.g. a portion which is exposed and not covered by any insulation materials) in direct physical contact with the round window membrane during use of the claimed apparatus (or in contact with tissue materials adjacent thereto which shall be deemed equivalent, namely, the mucosa/bone of the round window niche and others), evoked or non-evoked electrical potentials as defined above may be transmitted to and/or from the membrane for therapeutic analysis and other purposes using various techniques encompassed within the term xe2x80x9celectrocochleographyxe2x80x9d or xe2x80x9cECoGxe2x80x9d. Iontophoresis techniques may also be facilitated using the components listed above, with this term being defined to involve a process in which electrical energy is employed to alter the permeability characteristics of the round window membrane to achieve selective fluid transfer and the like. Furthermore, the elongate conductive member may also be used for the purposes listed above in connection with other middle ear tissue structures aside from the round window membrane in order to precisely monitor the tissue materials of interest.
In a still further variation of the claimed apparatus, all of the embodiments discussed above may likewise include at least one semipermeable membrane element operatively attached to the fluid transfer conduit at a position which will enable the membrane to at least partially block the fluid flow passageway(s) therein so that any of the fluid materials to be transferred through the passageway(s) will first need to pass through the membrane. The term xe2x80x9coperatively attachedxe2x80x9d as used herein shall involve a situation in which the membrane is attached in any manner (1) directly to and over the first and/or second end of the fluid transfer conduit; or (2) inside the passageway(s) of the conduit at any position therein. Accordingly, this embodiment of the invention shall not be restricted to any particular placement methods or positions relative to the semipermeable membrane unless otherwise noted herein. Many different materials may be employed in connection with the semipermeable membrane, with the claimed invention not being restricted to any particular construction materials for this purpose. These materials will be listed in the Detailed Description of Preferred Embodiments section. The semipermeable membrane is specifically designed to allow fluid materials (e.g. molecules) being transferred through the conduit to pass into or out of the conduit in a more controlled and uniform manner when desired (e.g. in the case of drug microdosing and other similar situations as discussed further below). In a preferred embodiment, the semipermeable membrane is attached to the end of the fluid transfer conduit that ultimately resides within the fluid-receiving zone located between the inflated bladder member and the round window membrane or other internal ear structure (regardless of whether the fluid-receiving zone is sealed or unsealed). While the use of a semipermeable membrane in connection with the fluid transfer conduit is optional, it is again noted that this particular component is prospectively applicable to all of the specific embodiments recited and covered herein.
At this point, a further discussion of the fluid transfer conduit is in order. As previously indicated, the fluid transfer conduit may consist of a single conduit member having a central passageway therethrough which is designed to accommodate both the delivery of fluid materials to the inner ear via the round window niche/round window membrane and the withdrawal of fluid materials from the inner ear which pass through the round window membrane. In addition to this single-conduit embodiment, the apparatus as claimed shall likewise encompass a system with multiple, individual conduits (e.g. two or more) each having a common (single) inflatable bladder member operatively connected to all of the conduits, with each of the conduits comprising a first end, a second end, and a passageway therethrough. One of these conduits may be used for fluid delivery, with the another conduit being employed for fluid extraction. As a result, cross-contamination of the fluid materials which are entering and leaving the inner ear is avoided which can be important in situations where therapeutic agents (e.g. drugs) need to be delivered in very precise (e.g. microgram, microliter, or nanoliter) amounts over controlled time periods. In a multi-conduit system of the type described above, any of the conduits may likewise include (1) the semipermeable membrane; and/or (2) the electrical potential transmission system associated therewith as previously discussed.
In a still further alternative embodiment, a single fluid transfer conduit may be employed which will nonetheless include multiple (e.g. two or more) passageways (or xe2x80x9clumenxe2x80x9d) therethrough, all of which are maintained separately from each other. One of these passageways may be used for fluid delivery, with another passageway being employed for fluid extraction. The use of a multiple passageway version of the claimed apparatus is again particularly important in situations where cross-contamination between (1) the fluid materials being delivered into the ear; and (2) the residual fluid materials being removed or exchanged is not desired. This type of system (which is readily manufactured using mass-production techniques) may be used in connection with all of the various bladder designs listed herein in order to provide either a partially or completely sealed fluid-receiving zone. The multi-passageway conduit may likewise include (1) the semipermeable membrane; and/or (2) the electrical potential transmission system associated therewith as previously noted. Either or both of these optional components may again be employed in connection with all of the embodiments discussed herein.
Regarding inflation of the bladder member using the selected inflation fluid (with the term xe2x80x9cfluidxe2x80x9d being defined above), many different approaches may be employed for this purpose with the present invention not being restricted to any particular inflation method(s). For example, the bladder member can be inflated before or preferably after insertion within the round window niche. Inflation of the bladder member after insertion is preferred since it minimizes frictional engagement between the claimed apparatus and the tissue structures of the middle ear. To accomplish inflation, the bladder member may be xe2x80x9cpre-inflatedxe2x80x9d during the manufacturing process and prior to attachment of this structure to the fluid transfer conduit (or conduits). Alternatively, the bladder member may be inflated during or after insertion of the apparatus into a patient using a separate xe2x80x9cinflation fluid delivery conduitxe2x80x9d operatively connected to the bladder member. This embodiment will allow the inflation fluid to be delivered directly from an external source into the interior region of the bladder member at a desired rate and amount (discussed further below).
Finally, an efficient, preferred, and space-saving embodiment of the invention will involve the use of a multi-passageway fluid transfer conduit in which one of the passageways is employed to deliver a selected inflation fluid to the bladder member. In this particular embodiment, the bladder member is in fluid communication with at least one of the above-listed passageways through the fluid transfer conduit which is selected for use in delivering the desired inflation fluid to the bladder member. Fluid communication between these components (e.g. the bladder member and the selected passageway within the fluid transfer conduit which shall be designated as an xe2x80x9cinflation fluid delivery passagewayxe2x80x9d) will be discussed in greater detail below. However, in a preferred form of the invention, the inflation fluid delivery passageway will terminate at an opening through the side wall of the fluid transfer conduit, with this opening being in substantial registry and communication with a corresponding opening through the main wall of the bladder member. In this manner, a selected fluid may be delivered at a controlled rate to the bladder member so that it can be inflated on-demand (or deflated by reversing this process). This particular embodiment also avoids the use of a separate stand-alone (e.g. exterior) tubular conduit for delivery of the inflation fluid to the bladder member. The inflation system described above may be employed in connection with all of the various bladder members listed herein in order to provide either a partially or completely sealed fluid-receiving zone. Likewise, the foregoing embodiment may optionally incorporate (1) the semipermeable membrane; and/or (2) the electrical potential transmission system associated therewith as previously noted.
All of the various embodiments of the present invention incorporate a common group of features, namely, at least one fluid transfer conduit having an inflatable bladder member operatively connected thereto which permits the claimed apparatus to be inserted and retained within the round window niche of a patient in a secure and minimally-invasive manner. By using the inflatable bladder system discussed above, dynamic (e.g. sliding) frictional engagement between the claimed apparatus and the tissues of the middle ear can be avoided which controls/reduces irritation, tissue damage, and patient discomfort. This type of system also facilitates orientation of the apparatus in a desired position within the ear using minimally-invasive endoscopic placement techniques and permits one device to fit many different-sized niches or cavities. Also, the system of the present invention enables a partially or completely sealed fluid-receiving zone (xe2x80x9cinner ear fluid transfer spacexe2x80x9d) to be formed between the bladder member and the round window membrane. As a result, the medicine delivery process (or desired fluid extraction procedure) can occur in a controlled manner which facilitates accurate microdosing, electrocochleography, and/or iontophoresis. This approach therefore represents an advance in the art of ear treatment, diagnosis, and analysis.
A brief summary of the procedures involved in transferring fluid materials into and out of the inner ear using the claimed systems will now be provided. The basic method to be employed in the present invention is equally applicable to all of the embodiments listed above and is likewise applicable to the transfer of fluid materials through all internal ear cavities (with primary reference to the round window niche as discussed below). Regardless of which apparatus is selected for use (e.g. a single fluid transfer conduit with a single passageway therethrough, a single conduit with multiple passageways, or multiple separate conduits), the desired apparatus having the features listed above is initially provided, followed by placement thereof in the middle ear of the patient. Specific methods for accomplishing this step (including the required microsurgical procedures) will be discussed further below in the Detailed Description of Preferred Embodiments section. Next, the bladder member and the portion of the fluid transfer conduit (or conduits) operatively connected thereto are at least partially inserted into the round window niche of the subject. The bladder member is then inflated as previously described using a selected inflation fluid (e.g. a liquid, gas, or gel) so that the bladder member at least partially engages the internal side wall of the round window niche. As a result, the bladder member and the portion of the fluid transfer conduit attached thereto are maintained at least partially inside the niche without requiring adhesives and other attachment systems. By inflating the bladder member after it is placed within the niche, dynamic (e.g. sliding) frictional engagement of the bladder member with middle ear tissues is avoided. This technique again reduces the possibility of frictional abrasion relative to the tissue materials of the middle ear and thereby minimizes (1) patient discomfort; (2) inflammation; and (3) the possibility of infection. However, it may likewise be possible to pre-inflate the bladder member prior to insertion within the round window niche and thereafter place the inflated bladder member inside the niche. The inflated bladder member will then compressively engage the interior side wall of the niche in order to again retain the claimed apparatus in a proper orientation/position within the middle ear. While inflation of the bladder member after insertion inside the niche is preferred for the reasons given above, it is important to emphasize that both inflation methods may be employed with a high degree of effectiveness and shall therefore be encompassed within the present invention as claimed.
Regarding inflation of the bladder member, this step may likewise be accomplished in many different ways as indicated above and further outlined in the Detailed Description of Preferred Embodiments section. The bladder member can again be pre-inflated during manufacture (and prior to attachment to the fluid transfer conduit) or inflated on-demand using a separate stand-alone conduit operatively connected at one end to a supply of inflation fluid and attached at the other end to the bladder member. However, in a preferred embodiment as previously noted, the fluid transfer conduit will include a plurality of passageways therein, one of which will be used to deliver a selected inflation fluid to the bladder member. In this particular embodiment, the bladder member is in fluid communication with the passageway selected for use in delivering the inflation fluid. The inflation fluid can then be transferred through the passageway (e.g. the xe2x80x9cinflation fluid delivery passagewayxe2x80x9d) and into the bladder member. As a result, the bladder member will inflate and at least partially engage the internal side wall of the round window niche so that a partially or completely sealed fluid-receiving zone or xe2x80x9cinner ear fluid transfer spacexe2x80x9d is created within the niche between the bladder member and the round window membrane. Whether the fluid-receiving zone is partially or completely sealed will depend on the configuration of the bladder member and the anatomical shape of the adjacent tissue structures under consideration.
After the claimed apparatus is properly inserted in position, the fluid materials of concern are appropriately transferred through the passageway(s) in the fluid transfer conduit as needed and desired. The terms xe2x80x9ctransferxe2x80x9d, xe2x80x9ctransferringxe2x80x9d, or xe2x80x9ctransferredxe2x80x9d shall encompass, without limitation, the movement of fluid materials in either direction within the fluid transfer conduit (e.g. either toward the round window niche/round window membrane or away from such structures). For example, these terms may involve the delivery of one or more therapeutic fluid compositions into and through the internal passageway(s) of the fluid delivery conduit (e.g. by conventional hypodermic delivery systems, microsyringes, osmotic mini-pumps, servosyringes, electromechanical pumps, and the like) so that the therapeutic fluid compositions pass through the fluid transfer conduit, enter the fluid-receiving zone within the round window niche, and come in contact with the round window membrane. The therapeutic fluid compositions will then pass through the round window membrane (by diffusion, osmosis, and the like) and move into the inner ear for the treatment thereof. Likewise, any residual fluid materials which remain or otherwise reside within the fluid-receiving zone between the bladder member and the round window membrane (e.g. residual, undiffused therapeutic agents, tissue fluids originating from within the inner ear, and the like) may thereafter or continuously be withdrawn through the internal passageway(s) of the fluid transfer conduit so that they can be removed from the patient. In one embodiment, the withdrawal of residual fluid materials as outlined above is accomplished by applying suction to the second end of the fluid transfer conduit which is remotely spaced from the bladder member and preferably positioned within the external auditory canal of the patient. Likewise, if dual internal passageways are used within the fluid transfer conduit, the delivery of various fluids through one passageway toward the round window membrane may, in fact, force any residual fluid materials already inside the fluid-receiving zone back through another passageway for withdrawal from the patient.
As previously noted, fluid materials can be transferred back and forth through the same internal passageway in a single-passageway conduit, through separate passageways if a multi-passageway conduit is employed, and through separate conduits in a multi-conduit system. Accordingly, the claimed method(s) summarized in this section are equally applicable to all embodiments of the invention.
If a selected electrical potential transmission system (e.g. an elongate conductive member) is used in connection with any or all of the claimed treatment units, electrical potentials (defined above) may be transmitted into and out of the inner ear via the round window membrane by placing at least a portion of the elongate conductive member against and in direct physical contact with the round window membrane. This can be accomplished by appropriate physical manipulation of the selected treatment apparatus within the middle ear as specifically discussed in the Detailed Description of Preferred Embodiments section so that the elongate conductive member comes in contact with the round window membrane. Electrical potentials received from the inner ear via the round window membrane and the elongate conductive member are especially valuable from a diagnostic standpoint, and are recorded/analyzed using an ECoG system operatively connected to the elongate conductive member. It should also be noted that the phrase xe2x80x9cdirect physical contact with the round window membranexe2x80x9d as it applies to the elongate conductive member shall include placement of this component against internal ear components selected from the group consisting of the round window membrane itself or ear tissue components adjacent to the round window membrane (e.g. the mucosa, bone tissues, and other similar structures which surround the round window membrane).
The use of a semipermeable membrane operatively attached to the fluid transfer conduit as discussed above will also provide a number of important benefits. In a preferred and non-limiting embodiment, the semipermeable membrane will be affixed to the end of the fluid transfer conduit that is ultimately positioned within the fluid-receiving zone between the bladder member and the round window membrane. In this manner, the semipermeable membrane will allow fluid materials being transferred through the conduit to pass into or out of the conduit in a more controlled and uniform manner when desired (e.g. in the case of drug microdosing and other similar situations).
Finally, while use of the present invention shall be discussed herein with primary reference to the round window membrane/round window niche, all embodiments of the invention are equally applicable to placement within other internal cavities in the middle or inner ear of a living subject (either natural or man-made), with examples of these other cavities being provided below. To use the claimed devices within other internal cavities in the ear, the procedures discussed above are followed which are incorporated by reference relative to internal cavities other than the round window niche. Specifically, in a preferred embodiment, the bladder member of the selected apparatus is at least partially placed into the desired internal cavity, followed by inflation of the bladder member in order to maintain the bladder member and the portion of the fluid transfer conduit operatively connected thereto at least partially within the selected internal cavity for the purposes listed above. The same procedure may be employed with a pre-inflated bladder member. Accordingly, unless otherwise stated herein, the present invention shall not be restricted to any particular location or environment within the ear of a living subject.
The present invention represents an advance in the art of inner ear therapy, treatment, and diagnosis. The claimed treatment systems and methods provide numerous benefits and capabilities including: (1) the creation of either a partially or completely sealed fluid-receiving zone (xe2x80x9cfluid transfer spacexe2x80x9d) within the round window niche of a patient which enables the controlled and effective delivery of therapeutic fluid compositions to the inner ear via the round window membrane; (2) the delivery of therapeutic fluid compositions to the inner ear using minimally-invasive approaches which are readily accomplished with minimum patient discomfort; (3) the transfer of a wide variety of different therapeutic agents into the middle and inner ear in a sustained, controlled, repeatable, and highly site-specific manner; (4) the removal of fluid materials from the inner ear, the round window niche, and adjacent tissue regions/structures in an efficient and thorough manner using a minimal amount of equipment and operating components; (5) the ability to electrocochleographically monitor evoked and non-evoked signals/potentials coming from the inner ear while simultaneously delivering therapeutic agents so that the effect of such agents can immediately determined before, during, or after delivery of the agents; (6) the more efficient use of iontophoretic techniques in inner ear therapy; (7) transmission into the middle and inner ear of various electrical signals for treatment purposes and/or the diagnostic, electrophysiological analysis of internal ear structures; (8) the ability to readily control placement of the claimed device within the round window niche of a patient using a highly specialized, fluid-inflatable xe2x80x9cplacement control systemxe2x80x9d in the form of a bladder member that is designed to engage the internal side wall of the round window niche (or other selected internal ear cavity); and (9) the development of a unique, multi-functional, xe2x80x9cone-size-fits-allxe2x80x9d inner ear treatment and diagnostic system which enables all of the foregoing benefits to be achieved using a minimal amount of components, procedures, equipment, and technical personnel. With respect to element number (8) listed above, this unique improvement enables the claimed apparatus to be more readily inserted and removed from a patient, and likewise secures the apparatus in position in a highly stable manner without requiring the use of adhesive compositions or other attachment systems. The invention as discussed herein is readily applicable to living subjects of different, age, size, and internal ear tissue configurations. For these reasons and the other reasons listed below, the claimed invention represents a substantial advance in the art of otological treatment and diagnosis.